The Nobel Prize for Medicine 2025 goes to three researchers who have discovered a decisive component of our immune system. Mary Brunkow, Fred Ramsdell and Shimon Sakaguchi have uncovered the mechanism of peripheral immune tolerance, which prevents our immune system from attacking the body’s cells and tissue. The decisive actors of this system are a certain gene on the X-chromosome and the regulatory T cells that control other defense cells and thus ensure that they do not attack our own tissues instead of microbial intruders. Since then we have known how the immune system friend of enemy distinguishes, at the same time the knowledge opened new approaches to the therapies.
Our immune system protects us from thousands of pathogens every day. The defense succeeds in recognizing the intruders despite their diverse characteristics as foreign and distinguishing them from body -owned cells. It has long been known that the T cells of the immune system play a key role. These defense cells go through a multi -stage training in the thymus, in which they learn to recognize the characteristics of the “enemies”, the so -called central tolerance. But as the three Nobel laureates have discovered this year, this is not all.
T-cells of a special kind
As early as the 1980s, Shimon Sakaguchi from the University of Osaka suspected that there must be another instance in the immune system that keeps the T-cells in check. Because in the central training in the thymus gland, there are always a few non -sufficient defense cells that can also attack the body’s own tissue. Sakaguchi followed his assumption in experiments with mice. He transferred mature or immature T cells from young mice with thymus to mice without this organ. He found that the thymusless mice got autoimmune diseases when they received immature T cells, but not when they got ripe T cells.
More detailed analyzes of these T cells reveal: In addition to the already known T-killer cells and T helper cells, there were some with an additional surface feature. In addition to the CD4 of the helper cells, these T cells carried the protein CD25 on their cell surface. The mouse tests suggested that these T cells do not activate, but braking on the other defense cells. In his view, this was the missing actor who protects us against autoimmune diseases and slow down insufficiently trained T killer cells. Sakaguchi therefore christened her regulatory T cells. But there were still doubts.
The FoxP3 gene and the immune regulation
The decisive next step was what Mary Brunkow and Fred Ramsdell, who at that time worked for the biotech company Celltech Chiroscience in the US state of Washington. At the end of the 1990s, they researched the question of why a certain mouse was particularly susceptible to autoimmune diseases. Through lengthy gene analyzes they tried to find out which gene mutation was responsible for this susceptibility.
In 2001 the two researchers found what they were looking for: in the middle of the X chromosome they discovered the gen FoxP3. This proved to be called IPEX not only for the autoimmune disease of the mice, but also for a rare autoimmune disease. But how was this gene change linked to the overly aggressive T cells of those affected? And where was the connection to Sakaguchi’s knowledge?
Shimon Sakaguchi was able to clarify this question two years later: he demonstrated that the Foxp3 gene controls the development of the regulatory T cells previously discovered. If this gene is defective, these cells and thus the actors, the other immune cells monitor and prevent them from attacks on the body’s own tissue. As Sakaguchi found, these regulatory ZT cells also ensure that our defense cell nach returns to the successful fight against microbial intruders.
Pioneering for autoimmun research and new therapies
Together, Brunkow, Ramsdell and Sakaguchi uncovered why we do not all suffer from autoimmune diseases and how the immune system keeps its T cells under control. Your findings have identified the phenomenon of peripheral tolerance and thus also paved the way to new medical treatments against cancer and autoimmune diseases.
“Your discoveries were crucial for our understanding of how the immune system works and why not all of us develop heavy autoimmune diseases,” says Olle Kämpe, chairman of the Nobel Committee.
Source: Nobelprize.org